There are many diseases, conditions, and syndromes where the propagation of electrical signals via neurological pathways may be hindered or inhibited, such as nerve entrapment syndromes, nerve compression nerve ischemia/infarct, radiation-induced injury, brain injury, brain diseases, brain disorders, inflammation, and degeneration.
To better understand the effect of diseases, conditions, and syndromes on neurological pathways, a basic understanding of the propagation of electrical signals within neural tissue will be helpful. Referring to FIG. 1, a typical neuron 1 that can be found in the white matter of the spinal cord or brain includes an axon 2 containing ionic fluid (and primarily potassium and sodium ions) 3, a myelin sheath 4, which is formed of a fatty tissue layer, coating the axon 2, and a series of regularly spaced gaps 5 (referred to as “Nodes of Ranvier”), which are typically about 1 micrometer in length and expose a membrane 6 of the axon 2 to extracellular ionic fluid 7. When an action potential (i.e., a sharp electrochemical response) is induced within the neuron 1, the transmembrane voltage potential (i.e., a voltage potential that exists across the membrane 6 of the axon 2) changes, thereby conducting a neural impulse along the axon neuron 1 as sodium and potassium ions flow in and out of the axon 2 via the membrane 6.
In particular, as shown in FIG. 2, when the axon 2 is at rest (point A), the interior of the axon 2 has a transmembrane voltage potential (i.e., the voltage potential of the interior relative to the exterior of the axon 2) of −70 to −80 mV. In response to a stimulation pulse (point B), which can be defined as an electrical signal that is large enough to evoke an action potential within the axon 2, the negative transmembrane voltage potential moves toward a more positive excitation threshold, thereby causing ionic current to inwardly flow into the axon 2, resulting in a change of the transmembrane voltage to a more positive value and approaching a threshold value (i.e., the transmembrane voltage potential at which an action potential is evoked, and in this case −55 mV) (point C). The transmembrane voltage potential then decreases rapidly, depolarizing axon 2 (high positive slope curve between point C and point D). Notably, the depolarization of the axon 2 is an all-or-nothing response (i.e., once the transmembrane voltage exceeds the threshold value, the action potential is propagated along the length of the axon 2). When the change in transmembrane voltage potential reaches a certain level (in this case 30 mV) (point D), ionic current outwardly flows out of the axon 2, resulting in a rapid change of the transmembrane voltage (becomes more negative), and repolarizing the axon 2 (negative slope curve between point D and point E). When the increase in transmembrane voltage potential reaches the resting voltage potential (point E), ionic current continues to outwardly flow out of the axon 2, thereby causing the negative change in the transmembrane electrical potential to continue beyond the resting electrical potential; that is, the axon 2 becomes hyperpolarized (point F). During this refractory period, the axon 2 returns to its resting period (point G) until another stimulation signal is applied to the axon 2.
Significantly, in myelinated axons, voltage-gated sodium channels (VGSCs), which are responsible for the initial inward current during the depolarization phase of an action potential (in excitable cells), are grouped in the nodes of Ranvier 5 (i.e., the areas between each myelinated section of the axon 2). Thus, because ion flow can only occur at the nodes 5 where the membrane 6 of the axon 2 is exposed to the extracellular ionic fluid 7, and due to the low capacitance of the myelinated sections of the axon 2, the neural impulse will actually jump along the axon 2 from one node 5 to the next node 5.
In this manner, the myelin sheath 4 serves to speed the neural impulse by insulating the electrical current and making it possible for the impulse to jump from node to node along the axon 2, which is faster and more energetically favorable than continuous conduction along the axon 2. Therefore, a small amount of charge (e.g., an action potential) may propagate a great distance along the axon 2.
Oftentimes, neurological conditions, syndromes, and diseases, such as multiple sclerosis and Guillain-Barre syndrome, cause demyelination of the axon 2, which can have devastating effects on behavior and neural function, because the lack of myelin slows down the conductions of, and may even block, action potentials that otherwise are conducted along axons within a nervous system. As an action potential moves from a myelinated region to a bare (demyelinated or damaged) stretch of axon, it encounters a relatively high capacitance and low transmembrane resistance. Therefore, the inward current of this area must flow for a longer time to supply enough charge to depolarize the next segment of the nerve in order to propagate the action potential. Because the body may not be able to produce the increased inward current necessary to propagate the action potential along the axon, neural signals are often slowed or blocked in demyelinated axons.
Furthermore, when damage to brain tissue occurs, a neuronal phenomenon referred to as “neuroplasticity” (variously referred to as “brain plasticity,” “cortical plasticity,” or “cortical remapping”) changes the organization of the brain in response to experiences. In most cases, neuroplasticity, as a natural process to compensate for a damaged region of the brain, is desirable. However, in some cases, neuroplasticity may not be desirable.
For example, the process of regenerating a severed nerve may be a long process. As such, it is important to maintain functionality of that nerve, as well as the cerebral neurons associated with the functioning of that nerve. However, without intervention, other neurological functions may take over those associated with the regenerating nerve via neuroplasticity. As another example, when someone loses the ability to hear, it is very important to get a cochlear implant as soon as possible so that neuroplasticity within the auditory sectors of the brain does not “erase” his or her ability to hear.
In some cases, neural tissue may be electrically stimulated to treat patients. While generally effective, the neural tissue may eventually accommodate to the stimulation, which entails a diminished neural response over time when there exists continuous input (in this case, electrical stimulation) due to cellular and synaptic mechanisms, thereby rendering the therapy less effective. For the purposes of this specification, the term “accommodation” generally refers to any mechanism that diminishes neural response due to continuous input.
There, thus, remains a need for an improved method and system that restores the ability of neurons affected by the aforementioned diseased states to efficiently propagate action potentials, and/or that prevents the occurrence of neuroplasticity, and/or prevents or reverses neurological accommodation.